Conditions such as trauma, tumours, cancer, periodontitis and osteoporosis may lead to bone loss, reduced bone growth and volume. For these and other reasons it is of great importance to find methods to improve bone growth and to regain bone anatomy.
Natural bone tissue formation from osteogenic cells with the aid of a three-dimensional scaffold offers an alternative to autografts and allografts to repair and regenerate lost bone. A well-constructed scaffold provides a suitable surface for cells to attach and adhere with a porous and well interconnected network guiding the development of new bone, supporting migration, proliferation and differentiation of bone-forming cells and vascularization of the ingrowth tissue. Although several polymers and bioceramics have been developed for their use in bone tissue engineering, their low mechanical properties have limited their use for load-bearing applications.
Titanium dioxide (TiO2) is a biocompatible material, which has also been reported to have bioactive properties and a certain degree of bacteriostatic effect. Therefore, ceramic TiO2 has been studied as a material for bone tissue engineering purposes. High porous and well-interconnected TiO2 scaffolds with high mechanical strength achieving values of 90% of porosity and of 1.63-2.67 MPa of compressive strength have been recently developed (Tiainen et al. 2010) and their biocompatibility and osteoconductive properties have been demonstrated in vitro and in vivo.
Attempts have been made to e.g. improve the scaffolds biocompatibility, to improve osseointegration, inhibit infection and inflammation by coating the implant structure with different kinds of biologically active molecules. However, in order to be able to perform their intended function on the implant after implantation, the biologically active molecules need to be coated onto the implant in a manner that allows their release, that does not detrimentally harm their biological activity and that does not cause negative body reactions etc.
Hydrogels have been used for different applications in tissue engineering such as space filling agents, as delivery vehicles for bioactive molecules, and as three-dimensional structures that organize cells and present stimuli to direct the formation of a desired tissue. A hydrogel typically comprises a network of polymer chains that are hydrophilic and highly absorbent and can contain over 99.9% water. Alginate is one example of a polymer chosen to form hydrogels for tissue engineering, having been used in a variety of medical applications including cell and/or growth factor encapsulation and drug stability and delivery. Alginate is a hydrophilic and linear polysaccharide copolymer of β-D-mannuronic acid (M) and α-L-glucuronic acid (G) monomers. Alginate gel is formed when divalent cations such as Ca2+, Ba2+ or Sr2+; cooperatively interact with blocks of G monomers creating ionic bridges between different polymer chains. Due to favorable properties for a biomaterial, such as nontoxicity, biodegradability, and ease of processing into desired shape under normal physiological conditions, alginate has been studied extensively in tissue engineering, including the regeneration of skin, cartilage, bone, liver and cardiac tissue.
Chitosan is the deacetylated derivative of chitin, a natural component of shrimp and crab shells. It is a biocompatible, pH-dependent cationic polymer, which is soluble in water up to pH 6.2. Chitosan is more stable than alginates, but are quickly broken down in low pH, e.g. conditions presents in inflamed, infected or hypoxic tissues. Chitosan itself is also believed to have anti-inflammatory properties. Other hydrogels like starches and collagen based gels have similar characteristics, but are more rapidly broken down by local tissue factors like collagenases. Celluloses are also pH dependent and can be fashioned in several different chemical modifications depending on the use, mechanical strength etc. needed. PLA and PGA are rapidly broken down to organic acids (i.e. lactic acid) that can have beneficial local effects on tissues, infections and on the breakdown rate of other hydrogels (e.g. chitosan) when used in combinations.
Hyaluronic acid is another important hydrogel with biological effects. It is an important constituent of cartilage and is commonly used in joints, for wound healing and in eyes. It is mildly anti-inflammatory and is believed to stimulate regeneration of certain types of connective tissues like cartilage, ligaments and corneal cells. PEG is a very biocompatible hydrogel that is highly flexible with regard to strength, crosslinking for designed break-down rates etc., and a gel that can be chemically linked to biological molecules to provide a controlled sustained release vehicle that can be designed for a multitude of conditions.
The mixing and gelling of some PEG differ from most other hydrogels in that it cannot simply be dissolved in water and allowed to gel in the presence of ions (like almost all biological hydrogels like chitosan, celluloses, starches, collagens, agaroses), but need a chemical reactant like mercaptoethanol to form stable crosslinks and become a gel.
However other PEG conjugates can also become gelated by different means such as UV light, crosslinking by ionic interactions, the addition of divalent cation salts and condensation reactions (condensation reactions between hydroxyl groups or amines with carboxylic acids or derivatives hereof are frequently applied for the synthesis of polymers to yield polyesters and polyamides, respectively, PEG).
However, there still is a need in the field of medical implants and tissue engineering for implant structures providing e.g. a supporting structure, which are biocompatible and/or which improve the Integration of the implant in a body.